Blood transfusion is an integral part in the management of sickle cell disease (SCD) patients. Alloimmunization is a recognized complication of red blood cell (RBC) transfusions with consequences including delayed hemolytic transfusion reactions and difficulties in getting compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in Uganda where pretransfusion screening for alloantibodies is not practiced.